Osmotic devices and other tablet formulations are known for their ability to provide a controlled release of a wide range of drugs. Such osmotic devices and other tablet formulations are disclosed in U.S. Pat. No. 4,014,334 to Theeuwes et al., U.S. Pat. No. 4,576,604 to Guittard et al., Argentina Patent No. 234,493, U.S. Pat. No. 4,673,405 to Guittard et al., U.S. Pat. No. 5,558,879 to Chen et al., U.S. Pat. No. 4,810,502 to Ayer et al., U.S. Pat. No. 4,801,461 to Hamel et al., U.S. Pat. No. 5,681,584 to Savastano et al., U.S. Pat. No. 3,845,770 and Argentina Patent No. 199,301, the entire disclosures of which are hereby incorporated by reference.
Osmotic devices have demonstrated utility in delivering beneficial active agents, such as medicines, nutrients, food, pesticides, herbicides, germicides, algaecides, chemical reagents, and others, to an environment of use in a controlled manner over prolonged periods of time. Known devices include tablets, pills, and capsules.
Advancements in the art have focused on developing osmotic devices with improved semipermeable or porous membranes, various coatings surrounding the core and/or the semipermeable membrane, layered osmotically effective agents in the core of the device, specific release profiles for specific active substances, and specific membrane or core compositions.
U.S. Pat. No. 4,931,285, U.S. Pat. No. 5,006,346 and U.S. Pat. No. 5,160,743 to Edgren et al., U.S. Pat. No. 5,160,744, U.S. Pat. No. 5,190,765 and U.S. Pat. No. 5,252,338 to Jao et al., U.S. Pat. No. 4,612,008, U.S. Pat. No. 4,765,989 and U.S. Pat. No. 5,082,668 to Wong et al., U.S. Pat. No. 4,327,725 to Cortese et al., U.S. Pat. No. 5,208,037 to Wright et al., U.S. Pat. No. 4,904,474 to Theeuwes et al. and U.S. Pat. No. 4,627,971 to Ayer disclose osmotic devices comprising a bi-layered core surrounded by a semipermeable membrane having at least one hole (or passageway). The bi-layered core, however, comprises a first push-layer containing no drug and a second layer containing drug. The hole(s) can be placed anywhere along the semipermeable membrane. These patents do not disclose a core having two different drug-containing layers, each providing a controlled release of drug through a respective hole in the semipermeable membrane.
U.S. Pat. No. 5,543,155 to Fekete et al. discloses an osmotic device comprising a bi-layered core surrounded by a semipermeable membrane having two holes (or passageways). The bi-layered core, however, comprises a first push-layer containing no drug and a second layer containing drug. The hole(s) can be placed anywhere along the semipermeable membrane. This patent does not disclose a core having two different drug-containing layers, each providing a controlled release of drug through a respective hole in the semipermeable membrane.
U.S. Pat. No. 4,662,880 to Hamel et al., U.S. Pat. No. 4,723,957, U.S. Pat. No. 4,867,969 and U.S. Pat. No. 4,971,790 to Magruder et al. disclose osmotic devices comprising a single-layered core surrounded by a semipermeable membrane having two oppositely placed holes. A drug-containing coat further surrounds the semipermeable membrane. These patents do not disclose a core having two different drug-containing layers, each providing a controlled release of drug through a respective hole in the semipermeable membrane.
U.S. Pat. No. 4,624,847 to Ayer et al. discloses an osmotic device comprising a semipermeable membrane surrounding a compartment that houses a drug-containing polymer that increases in size and releases drug. The semipermeable membrane has two oppositely placed holes for releasing drug. This patent does not disclose an osmotic device comprising core having two different drug-containing layers, each providing a controlled release of drug through a respective hole in the semipermeable membrane.
U.S. Pat. No. 4,915,954 to Ayer et al. and U.S. Pat. No. 4,814,181 to Jordan et al. disclose an osmotic device having a bi-layered core surrounded by a semipermeable membrane. The first layer comprises a first drug that is released from the core rapidly over a period of 2 min to 2 hr. The second layer comprises a second drug that is released from the core at a controlled rate over a long period of time. The layers of the core are in intimate contact and are not separated by another layer, lamina or membrane. The semipermeable membrane can have two holes, one hole adjacent each of the two layers of the core such that each layer releases drug through its own respective hole. The Ayer et al. and Jordan et al. patents do not disclose an osmotic device having a bi-layered core, wherein the layers are in contact with each other and in laminar arrangement with respect to one another and wherein each layer provides a prolonged and controlled release of an active agent.
U.S. Pat. No. 4,455,143 to Theeuwes et al. discloses an osmotic device having two compartments defined by a surrounding semipermeable membrane and a partition between the compartments. The semipermeable membrane has two oppositely placed holes, one for each compartment. Each compartment contains a drug that is delivered at a controlled rate through a respective hole in the surrounding membrane. The partition is required and retains its integrity during operation of the osmotic device.
U.S. Pat. No. 5,866,164 to Kuczynski et al. of Alza Corporation discloses an osmotic device having a bi-layered core surrounded by a semipermeable membrane. There is no partition between the layers. The core includes a drug-containing layer and a push-layer; and passageways in the surrounding semipermeable membrane only communicate the drug-containing layer, and not the push-layer, to the exterior of the device. This osmotic device was specifically designed to release only the drug in the drug-containing layer and retain the drug in the push-layer.
While the prior art discloses a wide variety of osmotic devices, none of the prior art discloses an osmotic device that provides a controlled delivery of at least two different active agents, wherein: a) the core of the osmotic device is bi-layered and comprises a first pharmaceutical composition in laminar arrangement with a second pharmaceutical composition; b) the pharmaceutical compositions are in contact with one another; and c) drug is released from each layer through a passageway in a surrounding membrane (coat).
None of the prior art discloses an osmotic device comprising a dual layered core, wherein each layer of the core provides a controlled release of its respective drug and wherein the layers are in direct (intimate) contact, i.e., the layers are not separated by a partition or another layer, and wherein neither layer is required to be a push-layer, per se.